1. Field of the Invention
This invention relates to novel 1,3-oxazolidine-2-one derivatives and more specifically to 1,3-oxazolidine-2-one derivatives each represented by the general formula (I): ##STR2## wherein R is a straight or branched alkyl group having 3 to 8 carbon atoms, X is a hydrogen or halogen atom or a lower alkyl or lower alkoxy group and n is an integer of 4 to 6, or acid addition salts thereof. Further, the invention relates to processes for the preparation of such derivatives.
2. Prior Art
It has been emphatically suggested that glutamic acid acts as an excitatory neurotransmitter at the central nervous systems of higher animals and at the neuromuscular junctions of lower animals ["Glutamate as a Neurotransmitter" edited by G. D. Chiara & G. L. Gessa, Raven Press, New York, 1981 and H. M. Gerschenfeld: Physiol. Rev., 53, 1-119 (1973)]. It has also been reported that dystropy, rigidity, tremor, convulsion and the like are induced from administration of kainic acid, domoic acid, quisqualic acid, ibotenic acid or the like, which acid is an extremely strong agonist for glutamic acid in higher animals [Oleny et al: Brain Res., 77, 507-512 (1974)].
It has also been known that as aging proceeds, the central and peripheral nervous systems undergo hypoergia to develop Parkinson's disease, mctoneuron disorders, dementia, tremor, spinocerebellar degeneracy the like. These diseases are considered to be attributable to off-balanced equilibration between excitatory nerves and inhibitory nerves (for example, the equilibration between glutamic acid and GABA) due to loss of neurons at certain specific sites or overall hypoergia of the nervous systems [Toshishige Hirai: Shinkei Shimpo, 17, 69 (1973)].
With the foregoing in view, medicines that can selectively block glutamic acid are useful for the therapy of neuropathy from which the senility would most often suffer and which would involve such complaints as vertigo, shoulder discomfort, convulsion, tremor and the like, all of them resulting from off-balanced nervous systems or hyperstenia in muscle discharge.
Glutamic aicd acts as an excitatory neurotransmitter for neuromuscular junctions of insects. Chemicals capable of blocking glutamic acid are also suitable for agricultural use for their ability to reduce and weaken insects' activities [Morifusa Eto: Kagaku to Seibutsu, 21, 725 (1983)].
Through intensive research leading to the invention, it has been found that 1,3-oxazolidine-2-one derivatives of the formula (I) above have excellent blocking effects against glutamic acid as well as neuraxial muscle relaxing effects, i.e. rigidity reducing and releasing effects on anemic decerabrate rigidity samples.
As compounds structurally similar to the compounds of the invention, there have previously been known 4-methyl-5-phenyl-3-(2-piperidinoethyl)-1,3-oxazolidine-2-one [Zikolova et al: Farmatsiya (Sofia), 14, 16-21 (1964) and Nikolova: Izv. Inst. Fiziol., Bulg. Akad. Nauk., 12, 217-226 (1969)] and 4-methyl-5-phenyl-3-(2-pyrrolidinoethyl)-1,3-oxazolidine-2-one [Zikolova et al: Farmatsiya (Sofia), 14, 16-21 (1964)].
However, Zikolova et al does not report anything about the pharmacological effects of these compounds. Nikolova reports that 4-methyl-5-phenyl-3-(2-piperidinoethyl)-1,3-oxazolidine-2-one has an analgesic effect, but exerts no anti-convulsion nor neuraxial muscle relaxing effects. In an experiment conducted by the inventors of this invention, the latter compound has been found to be extremely weak in its neuraxial muscle relaxing effect.